The goal of the proposed research is to determine the mechanisms responsible for the variation in transmitter release from the presynaptic nerve terminal that occurs during and following repetitive stimulation. The approach is to systematically characterize the processes (the first component of facilitation, the second component of facilitation, augmentation, potentiation, and depression) that are involved in transmitter release by developing a quantitative description of the processes and the relationship between the processes and transmitter release. Depending on the experiment, estimates of the relative amount of transmitter released at the vertebrate neuromuscular junction will be made from measurements of end-plate potentials recorded intracellularly or extra-cellularly or from measurements of end-plate currents recorded under voltage clamp. Models for the mechanism of transmitter release will be formulated and evaluated by comparing experimental results with predicted results obtained by simulation of the proposed mechanisms of release on a digital computer. Possible changes in the fine structure of the nerve terminal during and following repetitive stimulation will be examined to look for correlations to the changes in transmitter release.